Mycophenolic acid is a weakly-active antibiotic found in the fermentation broth of Penicillium brevi-compactum. Derivatives of mycophenolic acid, in particular, the morpholinoethyl ester thereof (i.e., MM) and certain simple ester derivatives of the phenolic hydroxyl group have been found to be effective in the treatment autoimmune disorders, psoriasis, inflammatory diseases (including in particular rheumatoid arthritis), tumors, viruses, allograft rejection, especially including cardiac allograft rejection, pancreatic allograft rejection and renal allograft rejection, and autoimmune diseases, including diabetes. When compared with mycophenolic acid, these ester derivatives show advantageous pharmacokinetic properties which enhance the systemic introduction of mycophenolic acid, for example, solubility in the delivery environment (e.g., the stomach), peak plasma concentration, maximum plasma concentration, and improved activity, e.g., anti-inflammatory activity.
Administration of therapeutic agents by intravenous formulation is well known in the pharmaceutical industry. An intravenous formulation should possess certain qualities aside from being just a composition in which the therapeutic agent is soluble. For example, the formulation should promote the overall stability of the active ingredient(s), also, the manufacture of the formulation should be cost effective. All of these factors ultimately determine the overall success and usefulness of an intravenous formulation.
MM in its monohydrate salt form is more stable than MM in its amorphous salt form, however the amorphous salt form has better solubility characteristics. It has been surprisingly found that a newly discovered crystalline anhydrous salt form of MM possesses about a two-fold increase in solubility over the monohydrate salt form, while possessing the same stability characteristics of the monohydrate salt form.